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Description of key information

Acute toxicity: via oral route

The harmonized LD50 cut-off valueof CR SB32N2 was 5000 mg/kg or Unclassified (OECD TG423).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 22, 2016 to June 06, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
- Source: BioLASCO Taiwan Co., Ltd (Taipei, Taiwan)
- Age at study initiation: 9-10 week old
- Housing: one or two animals per cage
- Diet: ad libitum
- Water: ad libitum
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Water for injection (WFI)
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
three
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.

Respectively, the mortalities andclinical observations in Dose Step 1 and 2 as below:

In Dose Step 1

No mortality occurred within the first three days post-dose. All dose animals tolerated the dose well and survived to termination on Day 15. Two animals (ID No. 0001 and 0003) were seen the excretion of feces of unusual color (deep pink), watery or unformed at 4 hours post dose. Animal ID No. 0001 also excreted watery brown feces at 0.5 hour post dose. Deep pink-stained skin over feet or tail was noted for all animal.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. One animal (ID No. 0004) was seen the excretion of feces of unusual color (deep pink), watery or unformed was seen at 4 hours post dose. Deep pink-stained skin over feet or tail was noted for two animals (ID No. 0004 and 0005). Other observations include the hair loss of the forelimbs for one animal (ID No. 0006). The small amount of hair loss was first observed on Day 1 and persistent to study completion.

 

In Dose Step 1 and 2, body weights increased throughout the study period and gross examination at termination revealed no remarkable changes or lesions in all dose animals.
Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 423 test method a, the harmonized LD50 cut-off value of CR SB32N2 was 5000 mg/kg. Therefore, CR SB32N2 was Category 5 or Unclassified based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316015-GN which is based on the SOP for the OECD 423 and OECD 423 (OECD, 2002). A total of 6 female Sprague-Dawley rats were orally dosed with CR SB32N2 in two dose steps of three animals each, at 2000 mg/kg b.w. for both Dose Step 1 and Dose Step 2. All animals in the two dose steps tolerated the test article well with increasing body weights and no mortality or moribundity reported. The remarkable clinical signs observed were excretion of deep pink feces in both dose steps on Dosing Day 1 and deep pink discoloration of the tail. Isolated instances of forelimb hair loss was also noted for one animal in Dose Step 2. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CR SB32N2 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Limited exposure evisaged.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on reliable review of literature and assessment of similar sulphonated azo dyes. No further animal testing is justified.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Methods not always explicit in reviews, but OECD testing principles appear to have been followed in most cases.
GLP compliance:
not specified
Test type:
other: Review of various studies
Limit test:
no
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
Mostly rat data, but dermal effects on guinea pigs and rabbits also examined (non-maximised sensitisation studies and dermal irritation)
Type of coverage:
not specified
Vehicle:
not specified
Doses:
Up to 2000 mg/kg
Control animals:
not specified
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality reported
Clinical signs:
Other than discolouration, no clinical signs
Gross pathology:
No adverse systemic effects reported.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on reliable review of literature and assessment of similar sulphonated azo dyes.
No further animal testing is justified.
Executive summary:

From assessment of similar substances and substances containing the same groups, none are noted as being acutely toxic and there is no evidence of dermal absorption. From various data sources, it is considered unlikely that the substance will be acutely toxic by the dermal route. Most dyes of this class have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

There is limited evidence that this type of substance is significantly absorbed by dermal contact due to the high molecular weight. Assessments of smaller molecules containing the same functional groups suggest low dermal toxicity.

 

It is not considered justifiable to perform further acute oral toxicity testing on CR SB32N2 in view of the similarity with other dyes assessed in this report.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
This class of substance considered to be of low toxicity and not likely to be absorbed dermally.

Additional information

Acute toxicity: via oral route

A total of 6 female Sprague-Dawley rats were orally dosed with CR SB32N2 in two dose steps of three animals each, at 2000 mg/kg b.w. for both Dose Step 1 and Dose Step 2. All animals in the two dose steps tolerated the test article well with increasing body weights and no mortality or moribundity reported. The remarkable clinical signs observed were excretion of deep pink feces in both dose steps on Dosing Day 1 and deep pink discoloration of the tail. Isolated instances of forelimb hair loss was also noted for one animal in Dose Step 2. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CR SB32N2 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Acute dermal toxicity

From assessment of similar substances and substances containing the same groups, none are noted as being acutely toxic and there is no evidence of dermal absorption. From various data sources, it is considered unlikely that the substance will be acutely toxic by the dermal route. Most dyes of this class have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

There is limited evidence that this type of substance is significantly absorbed by dermal contact due to the high molecular weight. Assessments of smaller molecules containing the same functional groups suggest low dermal toxicity.

 

It is not considered justifiable to perform further acute oral toxicity testing on CR SB32N2 in view of the similarity with other dyes assessed in this report.

Justification for selection of acute toxicity – dermal endpoint

Based on reliable review of literature and assessment of similar sulphonated azo dyes.

No further animal testing is justified.

Justification for classification or non-classification